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Radiochemotherapy Plus 3-aminopyridine-2-carboxaldehyde Thiosemicarbazone (3-AP, NSC #663249) in Advanced-Stage Cervical and Vaginal Cancers

Radiochemotherapy Plus 3-aminopyridine-2-carboxaldehyde Thiosemicarbazone (3-AP, NSC #663249) in Advanced-Stage Cervical and Vaginal Cancers

Charles A Kunos, Tomas Radivoyevitch, Steven Waggoner, Robert Debernardo, Kristine Zanotti, Kimberly Resnick, Nancy Fusco, Ramon Adams, Raymond Redline, Peter Faulhaber, Afshin Dowlati

Gynecol Oncol. 2013 Jul;130(1):75-80.

PMID: 23603372

Abstract:

Objective:
Cervical and vaginal cancers have virally-mediated or mutated defects in DNA damage repair responses, making these cancers sensible targets for ribonucleotide reductase inhibition during radiochemotherapy.
Methods:
We conducted a phase II study evaluating 3× weekly 2-hour intravenous 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, 25 mg/m(2)) co-administered with 1× weekly intravenous cisplatin (40 mg/m(2)) and daily pelvic radiation (45 Gy) in women with stage I(B2)-IV(B) cervical (n=22) or stage II-IV vaginal (n=3) cancers. Brachytherapy followed (40 Gy). Toxicity was monitored by common terminology criteria for adverse events (version 3.0). The primary end point of response was assessed by 3-month posttherapy 2-[(18)F] fluoro-2-deoxy-d-glucose positron emission tomography (PET/CT) and clinical examination.
Results:
3-AP radiochemotherapy achieved clinical responses in 24 (96% [95% confidence interval: 80-99%]) of 25 patients (median follow-up 20 months, range 2-35 months). 23 (96% [95% confidence interval: 80-99%]) of 24 patients had 3-month posttherapy PET/CT scans that recorded metabolic activity in the cervix or vagina equal or less than that of the cardiac blood pool, suggesting complete metabolic responses. The most frequent 3-AP radiochemotherapy-related adverse events included fatigue, nausea, diarrhea, and reversible hematological and electrolyte abnormalities.
Conclusions:
The addition of 3-AP to cisplatin radiochemotherapy was tolerable and produced high rates of clinical and metabolic responses in women with cervical and vaginal cancers. Future randomized phase II and III clinical trials of 3-AP radiochemotherapy are warranted.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP143621356	3-AP		143621-35-6	Price

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